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Department of Medicine

Department of Medicine

  Division of Rheumatology and Clinical Immunology

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photo Mandy J McGeachy, PhD

Associate Professor of Medicine

Email: mmcgeach@pitt.edu

Contact
Office: 3500 Terrace Street
BST South, S719
Pittsburgh, PA 15261
 
E-mail: mmcgeach@pitt.edu
Administrative Assistant:
Kim Reynolds
Email: kir4@pitt.edu
Phone: 412-648-9782
Education and Training
Education
BSc (Immunology), University of Glasgow, Scotland, UK, 2001
PhD (Immunology), University of Edinburgh, Scotland, UK, 2005
Training
Postdoc, Schering-Plough Biopharma/DNAX, 2009
Senior Scientist/Associate Principal Scientist, Merck Research Labs, 2011
Research Interest
Th17 cells cause chronic tissue inflammation in autoimmune diseases like psoriasis, multiple sclerosis and Crohn’s disease. However, Th17 cells and other ‘type-17’ cells provide vital protection against commensals and opportunistic pathogens at barrier surfaces, and also aid in wound repair. Many of these effects are achieved through IL-17. Perhaps due to these dual functions of Th17 cells, therapies targeted towards the IL-17 pathway are highly efficacious in some diseases, but have had mixed results in others. The McGeachy lab studies how inflammatory Th17 cells are generated, regulated and mediate their effects through IL-17 in different tissues, with the goal of determining the best approaches to modulate Th17-driven pathology while conserving the beneficial protective roles of Th17 cells.
Key questions being addressed:
1) Molecular mechanisms that regulate Th17 differentiation in humans, with a focus on the interplay between costimulatory and cytokine signaling;
2) Functional regulators of in vivo Th17 effector cell pathogenicity;
3) Regulation of Th17 migration in different tissues;
4) Th17:tissue interactions that lead to stromal cell remodeling during chronic inflammation .
Publications
For my complete bibliography, Click Here.
Selected Publications:
Shankar Revu, Jing Wu, Matthew Henkel, Natalie Rittenhouse, Ashley Menk, Greg Delgoffe, Amanda Poholek, Mandy McGeachy. IL-23 and IL-1b Drive Human Th17 Cell Differentiation and Metabolic Reprogramming in Absence of CD28 Costimulation. Cell Reports. 2018.
Verma, A.H., Richardson, J.P., Zhou, C., Coleman, B.M., Moyes, D.L., Ho, J., Huppler, A.R., Ramani, K., McGeachy, M.J., Mufazalov, I.A., Waisman, A., Kane, L.P., Biswas, P.S., Hube, B., Naglik, J.R., Gaffen, S.L. Oral epithelial cells orchestrate innate type 17 responses to Candida albicans through the virulence factor candidalysin. Science Immunology. 2017; 2(17): eaam8834.
Simon, D.W., McGeachy, M.J., Bayir, H., Clark, R.S.B., Loane, D.J., Kochanek, P.M. The far-reaching scope of neuroinflammation after traumatic brain injury. National Reviews Neurology. 2017; 13(9): 572.
McGeachy, M.J. A Hippo in the Fox(p3) house. National Immunology. 2017; 18(7): 709-711.
Hernandez-Mir, G, McGeachy, MJ. CD73 is expressed by inflammatory Th17 cells in experimental autoimmune encephalomyelitis but does not limit differentiation or pathogenesis. PLoS One. 2017.
Singh, D, Henkel, M, Sendon, B, Feng, J, Fabio, A, Metes, D, Moreland, LW, McGeachy, MJ. Analysis of CXCR5+Th17 cells in relation to disease activity and TNF inhibitor therapy in Rheumatoid Arthritis. Scientific Reports. 2016; 6: 39474.
Fang, D, Garg, AV, Kosar, K, Majumder, S, Kugler, DG, Mir, GH, Maggio, M, Henkel, M, Lacy-Hilbert, A, McGeachy, MJ. Inflammatory Th17 Cells Express Integrin avß3 for Pathogenic Function. Cell Reports. 2016; 16(5): 1339-1351.
Jain, R., Chen, Y., Kanno, Y., Joyce-Shaikh, B., Vahedi, G., Hirahara, K., Blumenschein, W.M., Sukumar, S., Haines, C.J., Sadekova, S., McClanahan, T.K., McGeachy, M.J., O'Shea, J.J., Cua, D.J. Interleukin-23-Induced Transcription Factor Blimp-1 Promotes Pathogenicity of T Helper 17 Cells. Immunity. 2016; 44(1): 131-142.
Garg, A, Amatya, N, Chen, K, Cruz, JA, Grover, P, Whibley, N, Conti, HR, Hernandez Mir, G, Sirakova, T, Childs, EE, Smithgall, TE, Biswas, PS, Kolls, JK, McGeachy, MJ, Kollatukudy, PE, Gaffen, SL. MCPIP1 endoribonuclease activity negatively regulates interleukin-17-mediated signaling and inflammation. Immunity. 2015; 43(3): 475-487.
Huppler, A.R., Whibley, N., Woolford, C.A., Childs, E.E., He, J., Biswas, P.S., McGeachy, M.J., Mitchell, A.P., Gaffen, S.L. A Candida albicans Strain Expressing Mammalian Interleukin-17A Results in Early Control of Fungal Growth during Disseminated Infection. Infect Immunology. 2015; 83(9): 3684-3692.
Sponsored Research/Activities
Title: Regulation of Th17 Functions in Autoimmune CNS Inflammation
Role: Principal Investigator
Funding Agency: National Institute of Allergy & Infectious Diseases
Grant Number: R01 AI110822
Start Year: 2014
End Year: 2019
Title: Regulation of Th17 Functions in Autoimmune CNS Inflammation
Role: Principal Investigator
Funding Agency: National Institute of Allergy & Infectious Diseases
Grant Number: R56 AI110822
Start Year: 2014
End Year: 2015
Title: IL-23 STAT3 Driven Oral Immune Responses to Candida Albicans
Role: Principal Investigator
Funding Agency: National Institute of Dental/Craniofacial Research
Grant Number: R01 DE023815
Start Year: 2013
End Year: 2018
Title: Identification of the PBMC Gene Signature that Predicts Requirement for Aggressive Therapy Such as Tofacitinib RA
Role: Principal Investigator
Funding Agency: Pfizer Inc.
Start Year: 2013
End Year: 2015
Title: A Novel Integrin Expressed by Th17 Cells in RA
Role: Principal Investigator
Funding Agency: Rheumatology Research Foundation
Start Year: 2013
End Year: 2014
Title: Host and Fugal Regulation of Type 17 Immunity to Oral Candidiasis
Role: Co-Investigator
Funding Agency: National Institute of Dental/Craniofacial Research
Grant Number: R01 DE022550
Start Year: 2017
End Year: 2022
Title: IL-17 Isoforms in Organ Specific Autoimmunity
Role: Co-Investigator
Funding Agency: National Institute of Allergy & Infectious Diseases
Grant Number: R21 AI128991
Start Year: 2016
End Year: 2018
Title: UPITT Rheumatoid Arthritis Combined Center (UPITT RACC)
Role: Co-Investigator
Funding Agency: National Institute of Arthristis, Muscoskel, & Skin Disease
Grant Number: UH2 AR067685
Start Year: 2014
End Year: 2017
Title: IL-17 Receptor Signaling in the Oral Mucosa (Administrative Supplement)
Role: Co-Investigator
Funding Agency: National Institute of Dental/Craniofacial Research
Grant Number: R01 DE022550
Start Year: 2013
End Year: 2017
Title: Rheumatoid Arthritis Comparative Effectiveness Research (RACER) Longitudinal Extension Study
Role: Co-Investigator
Funding Agency: Genentech, Inc.
Start Year: 2010
End Year: 2016
Notable Achievements
Member, American Association of Immunologists, 2011-present
Member, American College of Rheumatology, 2012-present
Member, International Cytokine and Interferon Society, 2013-present
International Cytokine and Interferon Society Young Investigator, 2013
Editorial Board Member, Cytokine, 2014-present
Editorial Board Member, Scientific Reports, 2015-present